Genetically Identical twins but only one gets cancer.
Genetically Identical mice but only one is obese.
The Placebo Effect is unanswerable to modern medicine and science. The Nocebo Effect as well.
Only some woman with the BRCA1 gene get cancer, others do not.
Cells without nuclei and DNA still live and behave as if they are whole.
The culture in the Petri dish determines how the genetically identical stem cells differentiate.
Without changing the DNA one iota, inheritable traits still get passed on; how is this so?
“I think there’s very little options for the DNA, there’s an awful lot of options for the epigenome layer,”
- David Allis, Ph.D.
Tri-Institutional Professor, Joy and Jack Fishman Professor
Laboratory of Chromatin Biology and Epigenetics
Today’s Science is Often Shortsighted. (It’s sights are on the status quo profits)
Science can be slow to change its paradigms of how we view our human world. There is an entrenchment into the current thinking due to the inherent need for homeostasis that our institutions lean to just as our bodies do. To upset the institutionalized system with new knowledge is to ask our institutions to change. To change can be dangerous and scary for the status quo. The change will always bring with it a death sentence to certain aspects of the old system, from jobs, to reputations, to shareholders and profits, to future contracts, to population control, to political lobbying and legislation, etc. In short, changes in scientific thinking can radically alter the foundation of life as we know it and hence, change is resisted vehemently, even in the face of logic and reason. In a refractive way, our immunological response to change in our bodies, our inherent army that fights what is not “host”, is also seen and felt keenly in our minds and thinking. This observation of refraction can help us understand why change in science can be slow to enter the main stream. In this paper I hope to elucidate a current scientific example of change being resisted; where the knowledge is already present, yet the world at large is still living in the old paradigm that is antiquated and incorrect.
One significant example of this resistance is the new knowledge and science of epigenetics. Epigenetics seems to have a variety of definitions, here are a few: “control of changes in gene function that do not involve changes in DNA sequences.” (1)- “in addition to changes in genetic sequence.”(2)- “of, relating to, or produced by the chain of developmental processes in epigenesis that lead from genotype to phenotype after the initial action of the genes” (3)- “An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence.” (4)- “Epigenetics literally means “above” or “on top of” genetics. It refers to external modifications to DNA that turn genes “on” or “off.” These modifications do not change the DNA sequence, but instead, they affect how cells “read” genes.” (5)- “Epigenetic: Something that affects a cell, organ or individual without directly affecting its DNA. An epigenetic change may indirectly influence the expression of the genome.” (6)- ; “changes in gene expression or cellular phenotype, caused by mechanisms other than changes in the underlying DNA sequence, that are passed from parent to offspring” (7). As the reader can see, there is a role interpretation of the word and its definition plays in the discourse about the science.
In today’s introduction to biology classes, in high schools and in colleges, students are being taught old school Newtonian models of a mechanistic universe whereby life is predetermined, alongside the “central dogma” of the Frank and Watson science that genes predetermine our biology, health, and physical expression and that DNA and its supposed random selection, control and limit our lives. While genetics undoubtedly play a strong role in our biology, it has already been shown that the interaction of the cell with what Max Plank termed the “matrix” or what is typically called the “field” in today’s world, is more fundamental in the cellular process of determination than any set preorder. Albert Einstein said “There is no place in this new kind of physics both for the field and matter, for the field is the only reality”. With the electro-magnetic field now emerging as the interface of human to nature and the interlocking of life, at the cellular level epigenetics is correlating the interface of cell to environment and its essential foundation of evolution. Epigenetics is showing that there is more to DNA expression than the old school has believed. The central dogma could never answer the puzzles to genetics listed above, and common sense could have told anyone asking, that there was more to evolution than the genetic determinism. Any parent for instance, could look at their own children and see how very different each child is even as they come from the same genetic inheritance. And to go further all one had to do was think of say Mozart’s child, genetically rich in genius musicianship genes, if put in Siberia without any music at all, would never realize his genetic potential. Simple thought experiments like this would inevitably lead a thinking person to see that genetics do not determine the evolution of the organism. Science sometimes leaves out, very erroneously, common sense.
In this paper I want to highlight the disservice education is laying on students by showing that the science of epigenetics needs to be taught along side with genetics in basic biology classes so that students understand that pharmaceutical medicines are not the only agents for change, but that prevention and treatment are strengthened when we understand how our environments affect our genetic expressions. In short I want to show how we can participate in the control of our cellular processes and not feel and think we are victims to our pre-set, at birth, genetic inheritance.
A Short History and Explanation of Epigenetics
Some say Epigenetics was coined over a century ago (8). One can go back as far as the early 19th century to find scientific postulates of what we now call epigenetics from Jean-Batiste Lamarck and what is called Lamarckism (9). Lamarck, who gave us the term biology , stated in his 1809 Philosophie zoologique: “The state in which we now see all the animals is on the one hand the product of the increasing composition of organization, which tends to form a regular gradation, and on the other hand that of the influences of a multitude of very different circumstances that continually tend to destroy the regularity in the gradation of the increasing composition of organization.” (10) What Lamarck refers to as “very different circumstances” that then change the trajectory of a geno/pheno-typical trend and hence alters what we now know and call genes, is an early iteration of what we now call epigenetics.
Unfortunately in a simple-minded experiment August Weisman, a contemporary of Lamarck, discredited Lamarck’s theory. Weisman conceived an experiment and put the matter to a practical test in a somewhat naïve or purposeful (let the reader decide) manner. He conducted an experiment in which he cut off the tails of 901 mice. Then with great thoroughness, he observed the next five generations of progeny. All the offspring grew normal tails and did not inherit the tailless characteristic of the parents. Hence Weismann was able to conclude, somewhat simply but ingeniously, that mutilations were not inherited. (11)
Epigenetics was actually initially coined by English biologist Conrad Hal Waddington (1942) to refer to the study of the “causal mechanisms” (environment et al) by which “the genes of the genotype bring about phenotypic effects.” What is now called developmental biology is the basis for how Waddington used his term epigenetics. He looked at “organizers and organizing relationships” that affected tissue and the development of that tissue thereof. In his textbook on developmental epigenetics, the term then meant the external manifestation of genetic activity. Waddington also believed that Neo-Darwinism involved “a breach between organism and nature as complete as the Cartesian dualism of mind and matter; an epigenetic consideration of evolution would go some way toward healing it.” And yet today, 70 years later, we still are living in a cultural paradigm of a split between the organism and the nature it spawns from, and a mind/matter division that keeps our views of separation and differentiation at the fore, rather than a more holistic view that unifies nature and nurture into an interdependent and relationship-based existence. (12)
Shifting the landscape: from central dogma to a developmental genome
In the 1960’s Dr. Bruce Lipton was working on adult stem cells and experimenting with their potentiality. His story is a familiar story to anyone interested in the science of epigenetics, which Dr. Lipton helped along through work that surprised even him, as he tells this story often in his workshops and interviews. He explains how his research revealed the science of epigenetics; “I placed one stem cell into a culture dish, and it divided every ten hours. After two weeks, there were thousands of cells in the dish, and they were all genetically identical, having been derived from the same parent cell. I divided the cell population and inoculated them in three different culture dishes. Next, I manipulated the culture medium—the cell’s equivalent of the environment—in each dish. In one dish, the cells became bone, in another, muscle, and in the last dish, fat. This demonstrated that the genes didn’t determine the fate of the cells because they all had the exact same genes. The environment determined the fate of the cells, not the genetic pattern. So if cells are in a healthy environment, they are healthy. If they’re in an unhealthy environment, they get sick.”
This simple story cannot be refuted and can be repeated over and over. The old scientific/medical model of “the central dogma” which Crick and Watson postulated in the late fifties, which states that the proteins of the nucleus determine the genetic expression, gets turned on its head with Dr. Lipton’s simple experiment. Dr. Lipton went further and removed the nucleus altogether from the cell, expecting the cell to die, as it was considered the “brain” or “command and control center” of the cell. What he found was that the cell could live on, for quite awhile actually. It could live until it needed the DNA to replicate and produce new proteins for the cell life. In this way he realized that the cell must be driven by something other than the nucleus since the cell can live without the nucleus and it’s DNA. He concluded that DNA is only needed for reproduction. Hence the nucleus of the cell is the gonad and not the brain of the cell. He went on to postulate that the brain of the cell is in fact the skin, the membrane, where the interface between the cell and its world takes place. The membrane has receptors and what gets received ultimately programs the cell.
The central dogma (the word dogma was later regretted by Crick as he really meant it as defined similarly to hypothesis, and not as a religious belief which cannot be doubted; an unfortunate choice which in hindsight has an ironic twist to it) emphasis on the proteins as the mediator of biological functions has been shown to be inaccurate. For example it is known that eighty percent of the human genome is transcribed yet only about one percent will code for proteins. There is research being done currently on the non-coding RNA that does not follow the central dogma path and does not code for polypeptides.
Dr. Lipton, like Lamarck before him, integrated the environment with the cell to be all apiece of a process, whereby Darwin demarcated lines which took the human out of its natural environment. “History has the habit of creating heroes and anti-heroes, and so Darwin triumphed while Lamarck bore the brunt of ridicule and obscurity. The reason is that the theories of the two men are logically diametrically opposed. Darwin’s theory is natural selection, and selection entails a separation of the organism from its environment. The organism is thus conceptually closed off from its experience, leading logically to Weismann’s barrier and the central dogma of the genetic paradigm, which is reductionistic in intent and in actuality. “(13)
Using the common sense logic noted above one could always ask how does the genius come to the fore when the parents are not in fact geniuses? Further how does the child of the genius, Mozart’s child, not become a genius himself? Transformations occur in childhood development that shifts the trajectory of one’s life. Circumstances like a world war will inevitably transform the evolution of a community and the individuals of it. The interchange and interactions of the individual personal life and the situations she lives in inevitably alter the course of one’s life and health, and thoughts, and talents, and all the physiology and psychology thereof. “Lamarck’s theory… is of transformation arising from the organism’s own experience of the environment. It requires a conception of the organism as open to the environment – which it actually is – and invites us to examine the dynamics of transformation, as well as mechanisms whereby the transformation could become ‘internalized’. Hence it leads logically to the epigenetic approach, which embraces the same holistic, systems thinking that Lamarck exemplifies.” (13)
Development is a process, alive and spontaneous and as unpredictable as the world we live in. We cannot predict the individual growth any more than we can predict the process of weather – they both are dynamic, ever changing processes which have many variables to consider. Even as we have methods for evaluating say the bone growth of an individual, as they do very well in ballet schools to determine the next ballerinas, the circumstances of that individuals’ life will determine what actually manifests; it is not a set course. “One important reason for focusing on development is that developmental changes are far from random or arbitrary. Instead, they are determined by the dynamics of developmental (epigenetic) processes which are amenable to mathematical description. The set of possible transformations is highly constrained so that particular transformations may be predictably linked to specific environmental stimuli. This is the basis for ‘structuralism in biology’, or ‘process structuralism’, which proposes a rational taxonomy of biological forms and a natural system of classification based on the dynamics of processes that generate the forms. The dynamics of the processes are themselves subject to contingent complexification in the course of evolution, by virtue of the lived experience of the organisms themselves. …directed genetic changes in given environments are proving to be just as nonrandom as morphological changes, and hence, possibly subject to comparable systemic constraints.” (14)
At this point one must ask and try to answer, if the genes do not need to be present for the cell to live and do all its work, what exactly is the driving force in this biological structuralism? If the cultural medium or the environment makes the genetic expression variable, what in the environment is triggering the genetic decision and how does the mechanism work?
This is where the old Newtonian mechanistic model of the universe also comes undone. Even today some molecular biologists look at the cell as a collection of protein making machines. But these models do not account for the creative decision making the cells and the body execute in living and maintaining the coherent state of homeostasis. The cell answers to its environment. Or perhaps better said, the cell communicates with its environment and chooses a direction, somehow, after evaluating or acknowledging the environmental factors. What caused Dr. Lipton’s identical cells to become different body parts? It can be supposed that the toxic environment which we know kills cells disallows the cell to do whatever it does in this decision making process. It can also be said that the immunological fight against varying destructive agents must be decided upon within a context of evolution and its trajectory. In other words, as new bacteria evolve for example, the body must evolve to create new fighting agents to continue homeostasis. How does this creative evolution of the cell happen?
How the Mechanisms of Epi-genetics Work
All the trillions of cells in an individual body carry every gene, but only few get turned on or activated. The complex system nature has evolved to allow certain genes to be accessed are a hallmark of biology. Gene regulation outside the cell is carried out by the DNA/histone protein complex called chromatin that parcels genetic information. Dr. Allis of The Rockefeller University is on the cutting edge of epigenetic research and has been studying the chromatin complex as he considers it the basis of epigenetics.
“Chromatin is the physiological template of the human genome. Elaborate mechanisms have evolved to introduce meaningful variation into chromatin to alter gene expression and other important biological processes. Three major mechanisms of this are covalent histone modifications, chromatin remodeling by ATP-dependent complexes and use of histone variants. Dr. Allis and his colleagues hypothesize that distinct patterns of covalent histone modifications form a histone or epigenetic “code” that is read by effector proteins to bring about distinct downstream events. Histone proteins, their posttranslational modifications and the enzyme systems responsible for generating them are highly conserved through evolution.”(15)
If the on/off switches of genetic decision making could be found that would be a huge advance in science and Dr. Allis is leading the charge. “The Allis lab is currently investigating different histone modifications and their biological roles in a variety of unicellular and multicellular eukaryotic models. Through such enzymatic processes as acetylation, methylation, phosphorylation and ubiquitylation, histones are believed to function like master on/off switches and determine whether particular genes are active or inactive.” (15) If doctors could learn how to turn on and off the genetic switches, they could intervene when an individual’s genome is analyzed and dangers of disease seem evident. Of course doctors could also use non pharmacological interventions as well, although the medical institutions like Rockefeller will not research these areas of study because little money is to be made; whereas synthesizing drugs and patenting them can generate vast amounts of wealth.
Epigenetics Today, 2012
In fact epigenetics is very alive and very interested in answering these newly arising questions. In spite of the fact that most high school and college students study biology and with it the genetic component of our human development, yet without the introduction to epigenetics. It appears that the study of epigenetics is limited to advance studies and mostly in elite universities. Even though epigenetics is hardly well known in the mass population, and even in high schools and colleges, there are epigenetic studies, textbooks, and courses available today. Below is a chart of high level institutions forging into the epigenetic universe for further exploration.
The relevance of epigenetics: (16)
|The top 20 institutions in the Special Topic of Epigenetics|
|1||JOHNS HOPKINS UNIV||21385||347||61.63|
|4||Univ So Calif||7355||114||64.52|
|9||UNIV CALIF SAN FRANCISCO||5286||146||36.21|
|11||UNIV CALIF LOS ANGELES||4907||120||40.89|
|16||COLD SPRING HARBOR LAB||4226||65||65.02|
|17||UNIV TEXAS HLTH SCI CTR HOUSTON||3939||152||25.91|
|18||Ohio State Univ||3926||152||25.83|
|20||UT SOUTHWESTERN MED CTR||3298||90||36.64|
Yet, these are highly specialized and advanced courses which most students would not have access to unless specializing in biology, genetics, development, etc. The average student will get biology of old. What are the ramifications of omitting this paradigm changing knowledge into current curriculums? Some are asking this question.
In psychology, the American Psychological Association published Genetics and epigenetics in the psychology classroom: How to teach what your textbook doesn’t (2013) The authors state: “Failure to teach psychology students about both genetics and epigenetics, however, means ignoring the latest research on nature versus nurture and not informing students about the next generation of tests and treatments for mental disorders.” And after elucidating the role of epigenetics in psychological development, they conclude “Given the link between biology and psychology, it is important for teachers of psychology to incorporate biological principles, including genetics and epigenetics, into their courses. Such topics are indispensable to our understanding of the relationship between nature and nurture. We encourage teachers of psychology to take advantage of the many resources available online and integrate them into their lessons.”(17)
Even the popular Time magazine offers a glimpse beyond what you may learn in college: see Why Your DNA is not Your Destiny – the New Field of Epigenetics is Showing How Your Environment and Your Choices Can influence Your genetic Code – And That Of Your Kids. (18)
Which begs the question, what is holding back education when the main stream is getting the information through commercial media? One conclusion might be that until epigenetics integrates wholly with the bio/pharmaceutical industry, when then money can be made from the drugs created; epigenetics will remain rather vague in the main stream. If the role of epigenetics were to be known widely before any drugs are patented to use for the learning, the main stream might actually take alternative approaches seriously. They might realize that foods, for instance can do what drugs do in the modifications of the cells and genes thereof. Much of the research today is funded by the pharmacology industry. The combination of our FDA and the big-pharma complex has been corrupting science for many years and has recently been taken to task by researchers from Harvard, York, and Rowan Universities. They have documented the abuses of the past decades and part of their thesis states, “The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised Congressional legislation to protect the public from unsafe drugs.” (37) Far from optimal, this kind of corruption interferes with the public getting the best of science and medicine.
The new edition of Epigenetic, a textbook by Cold Spring Harbor Press is a good example of an in-depth look into our subject by Rockefeller University. Its first edition was published in 2007 and its second edition is available now. (19)
In its description, it begins by stating “An understanding of epigenetics is central to research in transcriptional regulation, development, and disease.”
Regarding this last statement as true it seems unsuitable for biology students not to be introduced to epigenetics from the beginning of their study of biology. To learn the old, out-dated syllabus that keeps DNA as the “command and control center” of the regulation of the cell and development itself, does a huge disservice to students today and can almost be observed to be propagating an old paradigm for the sake of the status quo. For example, Human Biology, tenth edition, published by Brooks/Cole, a popular college level biology text, makes not one mention of epigenetics in its entire 700page plus book. (20) (As an aside, but interesting elaboration, Cengage Learning, of Brooks/Cole, filed for bankruptcy in 2013 to settle over 4 billion dollars in debts.) Here, as is the usual case, students will learn that DNA controls our bodies and that we are born with certain genetic traits and those traits are unalterable, although there is an interesting amount of noting that diet and exercise play a role, the thrust of the text is bio-pharmaceutical in nature and asks the reader to think of DNA as predetermined and to solidify the status quo of the day which victimizes the individual by its genes and then propagates the answers coming solely from the big-pharma machine of drugs and “immunizations” (another outdated topic that hides the relevance of current research to keep the status quo).
Despite the fact that text books and curriculums are leaving epigenetics out, PBS and its acclaimed series NOVA offers teachers a well planned teacher’s guide to teaching the role of epigenetics. In doing so they say, “Epigenetics is a highly relevant area, offering scientists new ways to investigate many fundamental questions about life, health, and disease. For example, how does a single fertilized egg cell differentiate into over 200 cell types? How do exposures to nutrients, toxins, pollutants, and other environmental agents affect gene expression? These questions are at the core of much of today’s cutting-edge research and technology in such fields as health care, medicine, pharmacology, fertility, and the management of environmental pollutants.” (21)
PBS also offers a multitude of resources on epigenetics. One example is a simple six minute video explaining epigenetic research from Madrid. In it a lead researcher states: “epigenomes can change in function of what we eat, of what we smoke or what we drink, and this is one of the key differences between epigenetics and genetics” (22)
What specifically is being left out of the introductory levels of development, be it biology, psychology, physiology, etc, is the epigenetic modification process of DNA. There are many ways the DNA is modified through epigenetics. One such process is methylation whereby a methyl group (-CH3) is added to specific cytosine bases of the four nucleotides (adenine, cytosine, guanine, thymine) traditionally taught in biology. This enzymatic process, DNA methylation, plays a key role, one of many, in development and in disease processes as it affects the way a molecule is shaped, which then affects its genetic expression or transcription. These changing substances, or agents, and the information within, lies just outside the DNA. The “outside” of the DNA is referred to as the Epigenome. Students who learn of this kind of DNA modification will have greater empowerment to stay healthy.
An example of this kind of education can be found in this interactive animation that helps students visualize how the degree of methylation can alter gene expression (i.e., how much protein is produced) can be found at the University of Utah Genetic Science Learning Center Gene Control website. (23)
This epigenetic process is a foundation of biology. It underlies the very existence of our genetic process. It is fundamental to the growing organism and is not something therefore to be learned after learning basic biology. This is somewhat like learning to dance without knowing there’s a layer of music that integrates with the movement, and motivates the choreography and its dynamics. The process is so ubiquitous it begins in meiosis and continues lifelong, and it isn’t that advance that a beginner student couldn’t understand it. “In eukaryotic cells, genomic DNA is wrapped around histone proteins to form nucleosomes, which together form chromatin fibers that can be further compacted into dense coils. Histone proteins can also be modified in a number of ways; in addition to methylation, they can be modified with acetyl groups (acetylation), phosphate groups (phosphorylation), ubiquitin proteins (ubiquitylation), and SUMO proteins (sumoylation). Epigenetic modifications to histone proteins can either inhibit or promote coiling or condensation of the chromatin. Collectively, these epigenetic modifications to DNA molecules and histones lead to changes in chromatin organization, which in turn affect how the associated genes are expressed, ultimately influencing an organism’s physiology and behavior. Recent discoveries also show that RNAs likely bind to histone proteins or help repress transcription of gene promoters, thereby modifying the cells.” (24) Students of biology can certainly understand this language and its concepts. (38)
The chromatin assemble and disassemble the DNA and are where the trigger points are where the gene becomes open to change or silenced to change via tight-wrapped chromatin that disallow the gene to be accessed. In the replication, half the histone proteins are from the parent cell and half are newly synthesized. And that process is being studied: “It has been of growing interest to understand how the parental pattern of epigenetic marks is re-established on the newly-synthesized histones, in a DNA sequence-specific manner, in order to maintain the epigenetic information through cell divisions. In this review we will discuss how histone chaperone proteins precisely coordinate the chromatin assembly process during DNA replication. We also discuss the recent evidence that histone-modifying enzymes, rather than the parental histones, are themselves epigenetic factors that remain associated with the DNA through replication to re-establish the epigenetic information on the newly-assembled chromatin. “(25)
Nature vs. Nurture?…The New Paradigm
Nature vs. Nurture arrives with a new twist when integrated into the epigenomic realities. No longer can the question be either/or, now the question is, how much of each? Even Nature, represented by the preset genetic code of an individual’s DNA after the parent’s combined chromosomes do their dance and finally come together with their 50/50 split inheritance, cannot be considered fixed, as it once was. The nature end of the question is the DNA, and come to find out, that is only a blueprint of possibilities. The genes are there in DNA code, like software in a computer, but the genes must get activated or turned on in order to express themselves and do their function, just like one’s computer software must have hardware to power it and turn it on; otherwise it is only a blank disc with a lot of information (binary code)stored. Software can only be as good as its hardware mechanisms driving it. Likewise DNA is only as good as the mechanisms that power it, the epigenome. If the hard drive is limited in RAM and processing speed, it will be only so able use the software so much. If the epigenome is limited in its nutrition it will only be able to utilize the DNA so much.
Think of your role with your computer, without you the computer is useless, it must be powered and driven by you, even if you program it to turn itself on and off and function while you’re away from it, it still required you to become active. In this way you are the Nurture side of your computer; it has its own nature and potential but it requires you to nurture it and how you nurture it will be reflected in how it expresses itself. In genetics, the DNA blueprint requires an outside force to interface with it to set it in motion. This outside force is the epigenome, and how it interacts with the DNA genes will determine the genetic activity. This insight is what has revolutionized genetics. “In the past 50 years, our growing understanding of epigenetics and its importance in development and disease has transformed how we think about the role of nature versus nurture. Clearly, epigenetic mechanisms are not strictly dictated by either of these two influences, and they have helped us reform our views regarding the role of nature versus nurture. With that understanding, scientists are realizing that epigenetic modifications have a powerful hand in the lives of organisms, as well as in the evolution of species. Indeed, without altering the identity of the DNA base pairs themselves, epigenetic modifications can shape many aspects of an organism’s phenotype.” (26)
Over the past decades much has been learned about how the epigenetic genome affects our health and development. How these effects get passed on is already known to a certain degree, and what lifestyle changes we can make that will inevitably affect our children are well documented in the main stream, only not under the guise yet of epigenetics. Hence the real importance of the real knowledge that we can change ourselves is shrouded in a mystique that we are still victims. Yet the nitty-gritty science is there and it is exciting to research. Even the details of the dance seem to come alive with explanation. “Once a gene has been methylated, all the daughter cells from that cell retain the methylation, making it a heritable change. Changes made to DNA are perpetuated every time the cell divides: eventually, many cells carrying the modification will exist. Age and environmental factors can change the amount of DNA methylation that occurs during a lifetime. Inappropriate methylation of genes is implicated in diseases such as cancer and atherosclerosis (hardening of the arteries). Some genetic conditions are caused by inappropriate over or under methylation of the same region of DNA, such as Prader-Willi and Angelman syndromes. Because DNA methylation can be affected by diet, stress and other environmental factors – including heavy metals, pesticides, diesel exhaust and tobacco smoke – it is one mechanism to explain how many dietary and environmental risk factors contribute to the development of cancer.” (27)
We are beginning to know the foods that help us avoid cancer, and again it would appear common sense would have signaled this long ago. Dark green vegetables absorb and contain wonderful minerals and vitamins from the soil, (if grown in fertile soil, and we have depleted our soil terribly with “conventional” farming). They also have great power from the sun and are rich in the sun’s healthy benefits. “To maintain normal DNA methylation patterns, several essential nutrients are required from the diet, including a source of methyl groups (eg, methionine or choline) and folate. Folate – found in green vegetables, legumes, oranges, and fortified juice and cereals – has attracted attention because a diet low in folate is thought to increase the risk of developing colorectal cancer. Phytochemicals are also being studied in mice and laboratory-grown cancer cells for their affect on DNA methylation. Genistein, one of the main phytochemicals in soy products, reactivates genes silenced by methylation and slows the growth of cancer cells. This is one mechanism proposed to explain why death rates from prostate cancer are low in men from countries with soy-rich diets, such as Japan.” (27)
And although some consider these mutations to be reset when meosis begins, “there is evidence that the methylation pattern of some genes can be inherited by offspring. This is causing a stir in biology, because it suggests that environmental stresses such as smoking or malnutrition experienced in a lifetime can have health impacts on that person’s descendants for several generations.” (27)
Exciting research is being done with most unconventional hypothesis because of the fact that epigenetics revolutionizes conventional thinking about genetics. One example is the study of a mother’s mood during pregnancy. Mood disorders are common with pregnant women today and if it is shown that the mother’s mood silences certain growth traits in embryonic cells it would be a remarkable piece of science that could be applied when advising and consulting mothers as well as treating them. “Exposure to maternal mood disorder in utero may program infant neurobehavior via DNA methylation of the glucocorticoid receptor (NR3C1) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), two placental genes that have been implicated in perturbations of the hypothalamic pituitary adrenocortical (HPA) axis. We tested the relations among prenatal exposure to maternal depression or anxiety, methylation of exon 1F of NR3C1 and 11β-HSD-2, and newborn neurobehavior. Controlling for relevant covariates, infants whose mothers reported depression during pregnancy and showed greater methylation of placental NR3C1 CpG2 had poorer self-regulation, more hypotonia, and more lethargy than infants whose mothers did not report depression. On the other hand, infants whose mothers reported anxiety during pregnancy and showed greater methylation of placental 11β-HSD-2 CpG4 were more hypotonic compared with infants of mothers who did not report anxiety during pregnancy. Our results support the fetal programming hypothesis and suggest that fetal adjustments to cues from the intrauterine environment, in this case an environment that could be characterized by increased exposure to maternal cortisol, may lead to poor neurodevelopmental outcomes.”(28)
The prefix “epi” means above, while “genome” refers to all of an individual’s genetic information. Thus, the epigenome is information about us that is stored outside, “above” our DNA —Specifically, special chemicals called “tags” or “marks” can become attached to the nucleotides of our DNA or to our histone proteins, and, depending on the nature of these tags, specific genes can either be silenced (prevented from being expressed as protein) or pushed to become more active (so that the abundance of a particular protein in our cells will rise). (29)
Tags that shut down, or silence, the expression of a gene include “methylgroups”. For example, the methylation (attachment of methyl groups) of tumor suppressor genes in cells infected with Epstein-Barr virus inactivates those genes, thereby promoting tumor formation. A second major type of tag, called an acetyl group, may be added to our histone proteins. The addition of acetyl tags (acetylation) weakens DNA-histone binding, making the DNA at that location more available to the proteins that drive transcription. For example, garlic has been shown to increase the acetylation (and therefore the activity) of anti-cancer genes. (29)
Studies have revealed that changes in the epigenome do not affect our DNA directly. That is, a change in the degree of methylation of a gene will not affect its nucleotides (i.e., instructions). It only affects the degree to which that gene will be translated into protein. Understanding how this occurs requires that we look again at transcription. To create an mRNA molecule, special enzymes in our cells must become attached to a gene at its starting point. When a gene is lightly methylated, these enzymes can access the starting point easily, whereas, in a heavily methylated gene, the DNA is more tightly wound, such that the starting point of the gene is more difficult to access. (29)
The Cancer Question: why do some people get it and others don’t even if genetically identical?
Cancer rates in this country and around the world are rising dramatically:
Key facts (30)
- Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (around 13% of all deaths) in 2008 (1).
- Lung, stomach, liver, colon and breast cancer cause the most cancer deaths each year.
- The most frequent types of cancer differ between men and women.
- About 30% of cancer deaths are due to the five leading behavioral and dietary risks: high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, alcohol use.
- Tobacco use is the most important risk factor for cancer causing 22% of global cancer deaths and 71% of global lung cancer deaths.
- Cancer causing viral infections such as HBV/HCV and HPV are responsible for up to 20% of cancer deaths in low- and middle-income countries.
- About 70% of all cancer deaths in 2008 occurred in low- and middle-income countries.
- Deaths from cancer worldwide are projected to continue rising, with an estimated 13.1 million deaths in 2030 (2).
- Deaths from cancer worldwide are projected to continue to rise to over 13.1 million in 2030.
With the rise of epigenetic science, cancer research and paradigms are changing rapidly. If the cell mutations that we call cancer are triggered from the “epi”, above the DNA, it presents itself as a wholly other phenomena than was previously thought which was that cancer was purely genetic, i.e. determined by the genes alone. Now that we understand that the genes are triggered to function based on outside, or above DNA mechanisms, then we have to look at the triggering mechanisms or causal agents of the activation of the genes. As was quoted at the top of this paper: there’s very little options for the DNA, there’s an awful lot of options for the epigenome layer. Since we know that greater methylation of the cells means greater silencing effect, what foods in our diets are methylating factors? And what foods might be acetylating? For example, garlic has been shown to increase the acetylation (and therefore the activity) of anti-cancer genes. We can look at exercise and distinguish the methylating and acetylating factors. Also, and very importantly, we can look at stress and how it affects our epigenome. Stress releases very profound and specific chemicals into our blood streams and we suffer great damage thereof. Could enough stress cause the kinds of genetic mutations cancer requires?
Dr. Bruce Lipton has been on the cutting edge of this research for a very long time. He postulates that our thoughts and beliefs trigger our epigenetic mechanisms in ways specific to the variance of our mental output: our wishes, dreams, hopes and fears, machinations, et.al. — be they conscious, or even more importantly, unconscious, or subconscious. He considers this material our programming, our software. And that programming is based in the foundation of our emotional/psychological habits and reflexes which were created in early life, even in the womb. When we consult with our psychiatrist and integrate the unresolved psychological material that has been repressed, for instance, we change our lives, the way we feel about ourselves, and our outlook towards the world. In short, we change our software. In so doing our physiology changes as well, as we now are not resorting to our brain stem and the automatic reflexes of unconscious programs but are now accessing our prefrontal cortex and activating new programming which is much more conscious and desired and hence the neurotransmitters that we activate are more optimal than before. We now are co-creating our health and vitality from a self-driven mind rather than the old habitual mind. “The chemistry of the body’s culture medium determines the nature of the cell’s environment within you. The blood’s chemistry is largely impacted by the chemicals emitted from your brain. Brain chemistry adjusts the composition of the blood based upon your perceptions of life. So this means that your perception of any given thing, at any given moment, can influence the brain chemistry, which, in turn, affects the environment where your cells reside and controls their fate. In other words, your thoughts and perceptions have a direct and overwhelmingly significant effect on cells.” (39) Instead of sending corticoids and adrenalines into our bloodstream, which cause us to experience fight or flight responses, we now send dopamine, epinephrine, serotonin and other feel good chemicals which will keep our system in the regenerative process of cellular repair and growth. Dr. Lipton presents an interesting new epigenetic paradigm that states that our perceptions and beliefs are the switches that turn our genes on and off.
Further ideas come from the ancient Hindu medicine called Ayurveda. Cancer doesn’t spread, according to Ayurvedic doctors, and it’s not a disease to them either. Instead they look at it as a survival mechanism. The body finds itself in a very toxic, acidified, oxygen depleted state and it creates cancer as a way to combat the toxicity. In Ayurvedic medicine the whole organism is treated including mind, body, and spirit, as all three affect our body’s chemical output that interfaces with our epigenome which then interfaces with our genome. Likewise the exterior environment is analyzed and treated to assist in reconstituting homeostasis and create a non-toxic, ph balanced, oxygen rich environment that will promote health and thereby shrinking tumors in cell growth. Recent research has shown that the ingredients in royal jelly are capable of inhibiting an enzyme called cytosine methyltransferase that methylates cytosine bases in honeybee DNA.
Also our government is aware and working on the epigenetic role of disease management… “How Genetics Affect Epigenetics: While epigenetics and genetics can cooperate in cancer initiation and progression, the interconnectedness between of these two processes is becoming increasingly apparent with the realization that several epigenetic modifiers are mutated in human cancers. Some examples of genetic mutations of epigenetic modifiers are shown in Table 1 and Figure 2.
The mutation of epigenetic modifiers presumably leads to profound epigenetic changes, including aberrant DNA methylation, histone modifications, and nucleosome positioning, although this remains to be demonstrated. These epigenetic alterations can lead to abnormal gene expression and genomic instability, which may predispose to cancer.” (31) The predisposition to cancer is being found to have profound implications. We can intervene and be sure the lifestyle can be adapted to suit the preference to defeat the chances of getting cancer.
At the esteemed Rockefeller University epigenetic scientists are leading the way toward new paradigms when it comes to cancer research. “It is clear that the regulatory signals provided by chromatin modifications will revolutionize our view of cancer as new models of epigenetic carcinogenesis are advanced. We favor the view that there exists an epigenetic indexing system for our genome, or a ‘histone code,’ that represents a fundamental regulatory mechanism that acts outside of the DNA itself.” (32)
Some doctors are leading the way to bring the new science of epigenetics to the people in simple and understandable manners. Even though the scientific jargon is absent the information is still accurate and enough for people to read and “get” and make changes accordingly. “In a nutshell, we all have tumor suppressor genes, and these genes are capable of stopping cancer cells in their tracks. These genes are present in every cell in your body, but so are proteins called “histones.” As Dr. Jean-Pierre Issa at the M.D. Anderson Cancer Center explainsv , histones can “hug” DNA so tightly that it becomes “hidden from view for the cell.” If a tumor suppressor gene is hidden, it cannot be utilized, and in this way too much histone will “turn off” these cancer suppressors, and allow cancer cells to proliferate. Now here’s where epigenetics comes in … certain foods, such as broccoli and other cruciferous vegetables, garlic, and onions contain substances that act as histone inhibitors, which essentially block the histone, allowing your tumor suppressor genes to activate and fight cancer. By regularly consuming these foods, you are naturally supporting your body’s ability to fight tumors.” (33)
The field of study called epigenetics is drastically altering our world view. It is a revolution in science that will shift the mindset of predetermined developmental philosophies to co-creating developmental philosophies. It removes victimization and explains the causal effects of disease and at the same time offers real data that we can indeed treat ourselves into health through healthy lifestyle living which includes body, mind, and spirit. “The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type-specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.” (34)
What we consider well-being, or the pursuit of happiness as a path toward a good life, has major implications for the role of health as epigenetics is proving. “People who have high levels of what is known as eudaimonic well-being — the kind of happiness that comes from having a deep sense of purpose and meaning in life (think Mother Teresa) — showed very favorable gene-expression profiles in their immune cells. They had low levels of inflammatory gene expression and strong expression of antiviral and antibody genes. However, people who had relatively high levels of hedonic well-being — the type of happiness that comes from consummatory self-gratification (think most celebrities) — actually showed just the opposite. They had an adverse expression profile involving high inflammation and low antiviral and antibody gene expression.” (35)
This epigenetic science also reveals again the interconnectedness of all, which contemporary physics is simultaneously revealing. The “matrix” of Max plank is coming to life in very real ways and epigenetics is a significant part of the emerging knowledge. It is a disservice indeed to not let our children know this new way of perceiving life and to allow them to wallow in the old dark days of genetic determinism and Darwinian evolution of survival of the fittest. They instead could be filled with the wonder of infinite possibilities toward making themselves into what they desire within the ranges of epigenetic possibilities. I believe this paper goes a long way to supporting this argument. I would love to see further research into what holds back the educational community from bringing cutting edge science that changes our world views to the classroom. With all this science already going on what other new discoveries will bring the co-creative power of the individual human and its community to new light?
On December 13, 2013, a friend sent me an email with the news of a second DNA code being discovered. This carries tremendous implications with it. Unfortunately this paper is not the place to delve further into it. So I will leave it as a teaser to be continued…”A second DNA code that was recently discovered by U.S. scientists has sparked a tremendous response from the worldwide scientific community. The second DNA code contains information that should shed new light on genetic mutations in health and disease development, reveals a study from the University of Washington which was published Thursday.” (36)
- -(Encarta online dictionary);
- (http://www.nature.com/scitable/spotlight/epigenetics-26097411) — Heidi Chial, Ph.D. (BioMed Bridge, LLC) and Jef Akst, M.A.